1. Field of the Invention
The invention relates to a novel strain of the Streptomyces genus and a method for producing antitumor aclacinomycins A, B, Y and aglycones by cultivation of the strain.
2. Description of the Prior Art
Aclacinomycins are a group of anthrocycline anti-tumor agents pyrrole and consists of three deoxypyranose residues. They exhibit cytotoxic activity by being intercalated into base pairs of DNA so that inhibiting synthesis of nucleic acid. Moreover, they selectively inhibit the synthesis of RNA unlike other anthracyclines such as daunorubicin, doxorubicin and canninomycin. Further, they are active against acute leukemia and malignant lymphoma while their cardiac toxicity is low.
Aclacinomycins may classified into three groups: aclacinomycins A, B and Y. They essentially have an aglycone residue, named as aklavine. Among them, aclacinomycin B had been scarcely employed in the clinics because it shows side effects and exhibits low antitumor activity. Aclacinomycin A has been practically employed due to its high anti-cancer or tumor activity low side effects and high yield of production. Aclacinomycin Y is expected to be the most useful anticancer agent since it shows considerably high antitumor activity and low side effects. However, its production yield from the culture broth of Streptomyces is low and it is required to improve the yield of the production.
A method for producing aclacinomycins by fermentation of Streptomyces galilaeus has been known (U.S. Pat. No. 3,988,315 to Hamao Umezawa). This patent reports that Streptomyces galilaeus produces about 18 analogues including aclacinomycins A, B and Y. However its production yield is very low: aclacinomycin A, a major product was produced in an amount of 46 mg/l culture broth, aclacinomycin B was produced in an amount of 23 mg/l and other products including aclacinomycin Y are produced in extremely small amounts. Accordingly, it is difficult to produce aclacinomycins in an industrial scale by using the above Streptomyces strain and there has been a need to provide a new strain which is capable of producing aclacinomycins in a high yield.
The present inventors had conducted extensive research to provide a process for producing aclacinomycins by fermentation in an industrial scale and as a result thereof had provided Streptomyces lavendofoliae 12/3A which is capable of producing aclacinomycins A and B. The present inventors made further researches for the purpose of providing an improved strain which produces larger amount of aclacinomycins and the purpose can be accomplished by the mutant Streptomyces lavendofoliae DKRS derived from the strain 12/3A.